• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

二茂铁基取代的姜黄素衍生物作为潜在的抗结直肠癌SHP-2抑制剂：设计、合成与评价

Ferrocenyl-Substituted Curcumin Derivatives as Potential SHP-2 Inhibitors for Anticolorectal Cancer: Design, Synthesis and Evaluation.

作者信息

Zhang Xing-Ze, Li Gen, Hu Gao-Yong, Wang Chen-Lin, Fang Yu-Qiu, Li Yuye, Qi Xue-Jie, Duan Lili

机构信息

Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P. R. China.

State Key Laboratory of Component-based Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P. R. China.

出版信息

ACS Omega. 2024 Dec 18;9(52):51701-51718. doi: 10.1021/acsomega.4c10629. eCollection 2024 Dec 31.

DOI:10.1021/acsomega.4c10629
PMID:39758657
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11696753/
Abstract

A panel of ferrocenyl-substituted curcumin derivatives has been designed and synthesized as protein tyrosine phosphatase proto-oncogene SHP-2 inhibitors. Antiproliferative activities of the synthesized compounds were tested against colorectal cancer cell lines (including RKO, SW480, and CT26). Compound showed excellent activities against the tested cell lines with IC values of 5.72, 3.71, and 1.42 μM. The cytotoxicity of compound was investigated on human normal colon epithelial cell line NCM460 with IC values of 929 μM compared to curcumin with IC values of 431 μM. The Western blot analysis approved that the expression level of SHP-2 in the CT26 and SW480 cell lines after being treated with was decreased, meanwhile it also affected the SHP-2 in tumor-associated macrophages (THP-1 and RAW264.7), which may support the suggested mechanism of as an SHP-2 inhibitor. Besides, could also inhibit the activation of the PI3K-Akt pathway in SW480 and CT26 cell lines and the tumor microenvironment (TME) by reducing the expression of PI3K and Akt proteins. Some cytokines (Arg-1, TGF-β, and IL-10) and chemokines (chemokine receptors and CC and CXC chemokine subfamilies) in the TME were also inhibited by . Finally, could increase the expression level of cell cycle-related and mitophagy-related proteins p27, PINK1, and Parkin and decrease the expression level of CDK1 and Cyclin-D1 proteins in CT26 and SW480 cells, which proved that could inhibit the proliferation of CRC cells through multiple pathways. Molecular docking studies against ALDH1 (PDB ID: 5ABM) revealed the good binding modes of the newly synthesized compounds.

摘要

设计并合成了一组二茂铁基取代的姜黄素衍生物作为蛋白酪氨酸磷酸酶原癌基因SHP-2抑制剂。测试了合成化合物对结肠癌细胞系（包括RKO、SW480和CT26）的抗增殖活性。化合物对测试细胞系表现出优异的活性，IC值分别为5.72、3.71和1.42 μM。研究了化合物对人正常结肠上皮细胞系NCM460的细胞毒性，IC值为929 μM，而姜黄素的IC值为431 μM。蛋白质印迹分析证实，用化合物处理后，CT26和SW480细胞系中SHP-2的表达水平降低，同时它也影响肿瘤相关巨噬细胞（THP-1和RAW264.7）中的SHP-2，这可能支持化合物作为SHP-2抑制剂的推测机制。此外，化合物还可通过降低PI3K和Akt蛋白的表达来抑制SW480和CT26细胞系及肿瘤微环境（TME）中PI3K-Akt信号通路的激活。TME中的一些细胞因子（精氨酸酶-1、转化生长因子-β和白细胞介素-10）和趋化因子（趋化因子受体以及CC和CXC趋化因子亚家族）也受到化合物的抑制。最后，化合物可增加CT26和SW480细胞中细胞周期相关和线粒体自噬相关蛋白p27、PINK1和Parkin的表达水平，并降低CDK1和细胞周期蛋白D1蛋白的表达水平，这证明化合物可通过多种途径抑制结直肠癌细胞的增殖。针对醛脱氢酶1（PDB编号：5ABM）的分子对接研究揭示了新合成化合物良好的结合模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/694bec444058/ao4c10629_0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/d2ef917114de/ao4c10629_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/b7bd4297e71f/ao4c10629_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/89dd58e7a995/ao4c10629_0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/a5a8b1773526/ao4c10629_0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/200152c9040a/ao4c10629_0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/d279f26381c4/ao4c10629_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/095194a36961/ao4c10629_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/8213aef37fd2/ao4c10629_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/6151bd052c43/ao4c10629_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/1fe0dfa93199/ao4c10629_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/ede675cbef1d/ao4c10629_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/feb00dbd5084/ao4c10629_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/4f5cb5bd2e8d/ao4c10629_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/694bec444058/ao4c10629_0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/d2ef917114de/ao4c10629_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/b7bd4297e71f/ao4c10629_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/89dd58e7a995/ao4c10629_0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/a5a8b1773526/ao4c10629_0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/200152c9040a/ao4c10629_0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/d279f26381c4/ao4c10629_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/095194a36961/ao4c10629_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/8213aef37fd2/ao4c10629_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/6151bd052c43/ao4c10629_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/1fe0dfa93199/ao4c10629_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/ede675cbef1d/ao4c10629_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/feb00dbd5084/ao4c10629_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/4f5cb5bd2e8d/ao4c10629_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22ce/11696753/694bec444058/ao4c10629_0011.jpg

相似文献

1
Ferrocenyl-Substituted Curcumin Derivatives as Potential SHP-2 Inhibitors for Anticolorectal Cancer: Design, Synthesis and Evaluation.二茂铁基取代的姜黄素衍生物作为潜在的抗结直肠癌SHP-2抑制剂：设计、合成与评价
ACS Omega. 2024 Dec 18;9(52):51701-51718. doi: 10.1021/acsomega.4c10629. eCollection 2024 Dec 31.
2
Molecular Docking and In Vitro Anticancer Screening of Synthesized Arylthiazole linked 2H-indol-2-one Derivatives as VEGFR-2 Kinase Inhibitors.合成芳基噻唑连接 2H-吲哚-2-酮衍生物作为 VEGFR-2 激酶抑制剂的分子对接和体外抗癌筛选。
Anticancer Agents Med Chem. 2022;22(11):2166-2180. doi: 10.2174/1871520621666211118102139.
3
Design, synthesis, and biological evaluation of symmetrical azine derivatives as novel tyrosinase inhibitors.新型酪氨酸酶抑制剂——对称嗪衍生物的设计、合成及生物学评价
BMC Chem. 2021 Sep 29;15(1):54. doi: 10.1186/s13065-021-00780-z.
4
Synthesis and evaluation of anticancer and antiobesity activity of 1-ethoxy carbonyl-3,5-bis (3'-indolyl methylene)-4-pyperidone analogs.1-乙氧羰基-3,5-双（3'-吲哚基亚甲基）-4-哌啶酮类似物的抗癌和抗肥胖活性的合成与评价
Bioorg Med Chem Lett. 2016 Mar 15;26(6):1633-1638. doi: 10.1016/j.bmcl.2016.01.073. Epub 2016 Jan 28.
5
Phthalazine Derivatives as VEGFR-2 Inhibitors: Docking, ADMET, Synthesis, Design, Anticancer Evaluations, and Apoptosis Inducers.作为血管内皮生长因子受体-2（VEGFR-2）抑制剂的酞嗪衍生物：对接、药物代谢动力学及毒性预测、合成、设计、抗癌评估和凋亡诱导剂
Drug Dev Res. 2025 Feb;86(1):e70037. doi: 10.1002/ddr.70037.
6
Design, synthesis and biological evaluation of a new series of thiazolyl-pyrazolines as dual EGFR and HER2 inhibitors.设计、合成及生物评价一系列新型噻唑基-吡唑啉衍生物作为双重 EGFR 和 HER2 抑制剂。
Eur J Med Chem. 2019 Nov 15;182:111648. doi: 10.1016/j.ejmech.2019.111648. Epub 2019 Aug 28.
7
Curcumol induces cell cycle arrest in colon cancer cells via reactive oxygen species and Akt/ GSK3β/cyclin D1 pathway.姜黄素通过活性氧和 Akt/GSK3β/细胞周期蛋白 D1 通路诱导结肠癌细胞周期停滞。
J Ethnopharmacol. 2018 Jan 10;210:1-9. doi: 10.1016/j.jep.2017.06.037. Epub 2017 Jul 4.
8
Design, Synthesis, and Antitumor Evaluation of 4-Amino-(1)-pyrazole Derivatives as JAKs Inhibitors.4-氨基-(1)-吡唑衍生物作为JAKs抑制剂的设计、合成及抗肿瘤评价
ACS Med Chem Lett. 2016 Aug 23;7(10):950-955. doi: 10.1021/acsmedchemlett.6b00247. eCollection 2016 Oct 13.
9
SHP-2-induced M2 polarization of tumor associated macrophages IL-4 regulate colorectal cancer progression.SHP-2诱导的肿瘤相关巨噬细胞M2极化 白细胞介素-4调节结直肠癌进展。
Front Oncol. 2023 Jan 26;13:1027575. doi: 10.3389/fonc.2023.1027575. eCollection 2023.
10
In-silico and in-vitro anti-cancer potential of a curcumin analogue (1E, 6E)-1, 7-di (1H-indol-3-yl) hepta-1, 6-diene-3, 5-dione.姜黄素类似物（1E，6E）-1,7-二（1H-吲哚-3-基）庚-1,6-二烯-3,5-二酮的计算机模拟和体外抗癌潜力
Biomed Pharmacother. 2017 Jan;85:389-398. doi: 10.1016/j.biopha.2016.11.040. Epub 2016 Nov 23.

引用本文的文献

1
Targeting SHP2: Dual breakthroughs in colorectal cancer therapy-from signaling pathway modulation to immune microenvironment remodeling.靶向SHP2：结直肠癌治疗的双重突破——从信号通路调节到免疫微环境重塑
World J Gastrointest Oncol. 2025 Jul 15;17(7):107380. doi: 10.4251/wjgo.v17.i7.107380.

本文引用的文献

1
Mechanism study of tyrosine phosphatase shp-1 in inhibiting hepatocellular carcinoma progression by regulating the SHP2/GM-CSF pathway in TAMs.酪氨酸磷酸酶shp-1通过调节肿瘤相关巨噬细胞中的SHP2/GM-CSF途径抑制肝癌进展的机制研究
Sci Rep. 2024 Apr 21;14(1):9128. doi: 10.1038/s41598-024-59725-w.
2
Targeting CDK1 in cancer: mechanisms and implications.靶向癌症中的细胞周期蛋白依赖性激酶1：机制与意义
NPJ Precis Oncol. 2023 Jun 13;7(1):58. doi: 10.1038/s41698-023-00407-7.
3
Macrophage-derived SHP-2 inhibits the metastasis of colorectal cancer via Tie2-PI3K signals.
巨噬细胞衍生的 SHP-2 通过 Tie2-PI3K 信号抑制结直肠癌转移。
Oncol Res. 2023 Apr 10;31(2):125-139. doi: 10.32604/or.2023.028657. eCollection 2023.
4
Methods to Improve the Solubility of Curcumin from Turmeric.提高姜黄中姜黄素溶解度的方法。
Life (Basel). 2023 Jan 11;13(1):207. doi: 10.3390/life13010207.
5
Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention.多酚作为肝脏保护和肝癌预防中潜在的代谢机制调节剂。
Cell Prolif. 2023 Jan;56(1):e13346. doi: 10.1111/cpr.13346. Epub 2022 Oct 13.
6
PTPN2 in the Immunity and Tumor Immunotherapy: A Concise Review.PTPN2 在免疫和肿瘤免疫治疗中的作用：简要综述。
Int J Mol Sci. 2022 Sep 2;23(17):10025. doi: 10.3390/ijms231710025.
7
Forever young: the first seventy years of ferrocene.永远年轻：二茂铁的七十年。
Dalton Trans. 2022 May 31;51(21):8085-8102. doi: 10.1039/d2dt00903j.
8
Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases: Status, Limitations and Countermeasures.姜黄素在炎症性疾病中的抗炎作用：现状、局限性和对策。
Drug Des Devel Ther. 2021 Nov 2;15:4503-4525. doi: 10.2147/DDDT.S327378. eCollection 2021.
9
The Interaction Between the Microbiome and Tumors.微生物组与肿瘤的相互作用。
Front Cell Infect Microbiol. 2021 Aug 31;11:673724. doi: 10.3389/fcimb.2021.673724. eCollection 2021.
10
The Role of Tumor Associated Macrophages (TAMs) in Cancer Progression, Chemoresistance, Angiogenesis and Metastasis - Current Status.肿瘤相关巨噬细胞（TAMs）在癌症进展、化疗耐药性、血管生成和转移中的作用——现状。
Curr Med Chem. 2021;28(39):8203-8236. doi: 10.2174/0929867328666210720143721.